Spatial, Temporal, and Dose Control of Drug Delivery using Noninvasive Magnetic Stimulation

Abstract

Noninvasive stimuli-responsive drug delivery using magnetic fields in conjunction with superparamagnetic nanoparticles offers the potential for the spatial and temporal control of drug release. When hyperthermia is not desired and control of the dosage is required, it is necessary to design a platform in which local heating on the nanoscale releases the therapeutic cargo without the bulk heating of the surrounding medium. In this paper, we report a design using a stimuli-responsive nanoparticle platform to control the dosage of the cargo released by an alternating magnetic field (AMF) actuation. A core@shell structure with a superparamagnetic doped iron oxide (MnFe2O4@CoFe2O4) nanoparticle core in a mesoporous silica shell was synthesized. The core used here has a high saturation magnetization value and a high specific loss power for heat generation under an AMF. The mesoporous shell has a high cargo-carrying capacity. A thermoresponsive molecular-based gatekeeper containing an aliphatic azo group was modified on the core@shell nanoparticles to regulate the cargo release. The mesoporous structure of the silica shell remained intact after exposure to an AMF, showing that the release of cargo is due to the removal of the gatekeepers instead of the destruction of the structure. Most importantly, we demonstrated that the amount of cargo released could be adjusted by the AMF exposure time. By applying multiple sequential exposures of AMF, we were able to release the cargo step-wise and increase the total amount of released cargo. In vitro studies showed that the death of pancreatic cancer cells treated by drug-loaded nanoparticles was controlled by different lengths of AMF exposure time due to different amount of drugs released from the carriers. The strategy developed here holds great promise for achieving the dosage, temporal, and spatial control of therapeutics delivery without the risk of overheating the particles’ surroundings.

Advances of Nano-Structured Extended-Release Local Anesthetics

“…However, ultrasound signal can be influenced by air attenuation and bone structure. Magnetic responsive nanoparticles exhibit broader application such as in respiratory system which is filled with air and central nervous system covered with cranial bone [143]. Furthermore, magnetic responsive nanoparticles can help spatially and temporally localize actives without restriction by tissues depth [143].…”

“…Magnetic responsive nanoparticles exhibit broader application such as in respiratory system which is filled with air and central nervous system covered with cranial bone [143]. Furthermore, magnetic responsive nanoparticles can help spatially and temporally localize actives without restriction by tissues depth [143]. Generally, there are three mechanisms underlying magnetic response, which are magnetic deformation, magnetic guidance, and magnetic-induced hyperthermia [144,145].…”

“…In contrast, chitosan-based nanoparticle undergoes pore formation with the help of heat produced by magnetic field [147,148]. In order to decrease thermal damage to surrounding tissues, Wei Chen and his colleagues produced a core-shell structure to embed heat-producing core and prevent thermal damage [143]. The guidance function can help the nanoparticle migrate long distance and penetrate biological barrier [149].…”

Plasmonic Cell‐Derived Nanocomposites for Light‐Controlled Cargo Release inside Living Cells

“…External stimuli such as ultrasounds, light or magnetic fields, are powerful, versatile external triggers to achieve spatiotemporal‐controlled drug delivery from artificial carriers in living systems 17. Such stimuli have been typically used to promote intracellular delivery of small molecules such anticancer drugs from plasmonic,18 magnetic,19 and ultrasound‐sensitive20 carriers. Examples of external‐stimulus‐controlled delivery of large macromolecules such as proteins (e.g., Abs), however, are scarce.…”

Tearable and Fillable Composite Sponges Capable of Heat Generation and Drug Release in Response to Alternating Magnetic Field

“…It has been reported that the combination of chemotherapy and thermal treatment, enhances treatment efficacy [24,25]. Notably, magnetic nanoparticles and anticancer drug-loaded materials can be used in a way to exploit the heat generated by magnetic nanoparticles in response to alternating magnetic field (AMF) exposure [26][27][28][29], which can subsequently act as a trigger for releasing drugs from the materials, achieving a remotely controllable on-demand administration of combined chemotherapy and thermal treatment [30][31][32][33][34].…”